The inflammatory response has an important role in the pathophysiology of diabetic nephropathy that is contributed to by inflammatory mediators such as interleukin-1 (IL-1), IL-6, IL-18, tumor necrosis factor-α, and macrophage chemotactic protein-1; however, the role of IL-18 seems to be more specific than other cytokines in the inflammatory process.
In addition, the levels of inflammatory factors (IL-1β and Cx43) and apoptotic markers (Caspase-3, and TUNEL) were significantly increased in d-USC compared to USC (<i>p<0.01</i>).
Immunostaining of such kidney biopsies across a broad spectrum of diabetic kidney disease stages revealed IL-1β positivity in a small subset of infiltrating immune cell.
This study evaluated whether an intensive lifestyle intervention (IL-I) targeting weight loss and inflammation through increased physical activity and reduced caloric intake can delay DN progression.
In addition, we discovered that mtROS overproduction is also associated with increases in NLRP3/IL-1β and TGF-β expression in the kidneys of patients with DN and db/db mice.
Inflammatory cytokines such as interleukin 1 (IL-1), IL-6, IL-18 and tumor necrosis factor-α (TNFα) have been linked to the development and progression of DN.
miR-21 expression was upregulated in serum and kidney tissues of DN patients, kidney tissues of STZ-induced DN rats, and HG-treated podocytes. miR-21 depletion inhibited pro-inflammatory factor (IL-1β, TNF-α) secretions and alleviated kidney damages in STZ-induced DN rats.
The serum levels of IL-18 and IL-1β in the DN group were the highest at 218.53±30.69 pg/mL and 62.47±9.36 pg/mL, respectively; followed by the mild DN group at 177.07±32.88 pg/mL and 28.13±5.37 pg/mL, respectively, with the diabetic mellitus (DM) group having the lowest levels at 141.47±9.49 pg/mL and 15.53±3.26 pg/mL, respectively.
Notably, IL-22 drastically reversed renal activation of NLRP3, cleavage of caspase-1, and the maturation of IL-1β in DN, suggesting unexpected anti-inflammatory function of IL-22 via suppressing the activation of NLRP3 inflammasome in vivo.
This study demonstrates NLRC4-driven IL-1β production as critical for the progression of DN, which underscores the importance to target this pathway to alleviate this devastating disease.
The present candidate-gene association study was conducted to investigate the association between the IL1BC-511T variant and the risk of DN in a Caucasian population.